The long-term goal of the proposed research is to develop hypotheses about the role of nutrition during lactation that are relevant to and ethically testable in human populations. This research will continue our study of this subject using the rat as a model. The first experiment will examine the basis for our finding that the period between peak lactation and the next conception is important for the renewal of maternal resources necessary to support subsequent lactation. It is hypothesized that chronically underfed dams gain fat during this period and exhibit increased lipogenesis and decreased lipolysis compared to controls. Adipocyte size and number also will be investigated. The remaining experiments will use a factorial design that permits examination of the effects of the timing of food restriction on outcomes of interest and includes four dietary treatment groups: fed ad libitum, fed ad libitum from a month before breeding until parturition and then food restricted (acutely restricted), food restricted throughout the experiment (chronically restricted), and food restricted until parturition and then fed ad libitum (refed). These experiments will examine the physiological and biochemical bases for our findings on the effects of malnutrition on hormones important for lactation, organ blood flow, and milk yield and composition. It is hyothesized that (1) prolactin values respond to suckling differently in control and chronically malnourished rats and that the vigor of the pups is a determinant of this response; (2) the effect of malnutrition on the values of prolactin, corticosterone, insulin and thyroid hormone differs over the course of lactation; (3) malnutrition will cause a reduction in the uptake of substrates for milk biosynthesis from the circulation (measured by blood flow to the mammary gland in conjunction with arteriovenous differences across the mammary gland), and (4) malnutrition will cause reduced rates of biosynthesis of milk macronutrients (measured in vivo following injection of radiolabelled precursors and subsequent isolation of lactose and lipid as well as in vitro in isolated mammary gland acinar cells).